Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia
- Conditions
- Thiazide-induced Hyponatremia (TIH)
- Interventions
- Other: Data and biosample collection
- Registration Number
- NCT05542056
- Lead Sponsor
- University Hospital, Basel, Switzerland
- Brief Summary
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment.
- Detailed Description
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. They act by inhibiting the apical Na+-Cl- -cotransporter in the distal convoluted tubules of the kidneys. Thiazides and thiazide-like diuretics often cause adverse effects, importantly a drop in plasma sodium levels that is called thiazide-induced hyponatremia (TIH). Data suggest a crucial role of urinary PGE2 in water reabsorption. Since urinary PGE2 concentrations were higher in patients with TIH, quantification of urinary PGE2 prior and after thiazide initiation might allow identification of patients at risk for TIH, presenting PGE2 as a potential novel predictive marker for the development of TIH.
This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment. Hospitalized and ambulatory patients in whom a thiazide or thiazide-like diuretic will be newly prescribed are screened for inclusion.
The study procedure contains the screening and inclusion, visit 1 before thiazide initiation, visit 2 4 weeks (+/-7days) after thiazide initiation and a 3-months follow-up (visit 3). An additional visit (visit 2.1) will only be added in case of a dose change of the thiazide or thiazide-like diuretic (4 weeks +/- 7 days after the dose change). The 2 hours- challenge is optional if the patient agrees to additional testing.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 232
- Newly prescribed thiazide or thiazide-like diuretic
- ≥ 18 years of age
- Informed Consent as documented by signature
- Intake of thiazide or thiazide-like diuretic in the preceding month
- Hyponatremia (plasma sodium <135 mmol/L) at baseline
- Acute infectious / inflammatory disease (CRP ≥ 20 mg/L [1, 11])
- Symptomatic urinary tract infection
- Chronic treatment with NSAID and / or NSAID intake 48 hours prior to urine sampling at visit 1 and 2 (intake of acetylsalicylic acid will be no exclusion criteria)
- End of life care, no informed consent or inability to follow the procedures of the study, e.g., due to language barriers, psychological disorders, dementia
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients with newly prescribed thiazide or thiazide-like diuretic Data and biosample collection As the study population of this observational study shall be as representative as possible all patients with a new thiazide or thiazide-like diuretic regardless of the indication, co-morbidities and co-medication can be included.
- Primary Outcome Measures
Name Time Method Occurrence of hyponatremia (plasma sodium <135 mmol/L) Within the first four weeks of treatment (at visit 2) Occurrence of hyponatremia (plasma sodium \<135 mmol/L)
- Secondary Outcome Measures
Name Time Method Change in systolic and diastolic blood pressure Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months Change in systolic and diastolic blood pressure
Incidence of hospitalization due to any cause Between baseline and visit 3, approximately 3 months Incidence of hospitalization due to any cause
Change in Bioelectrical impedance analysis (BIA) Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months Change in Bioelectrical impedance analysis (BIA)
Change in potassium Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in potassium
Change in uric acid Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in uric acid
Change in daily fluid intake Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months Change in daily fluid intake
Change in chloride Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in chloride
Incidence of fractures Between baseline and visit 3, approximately 3 months Incidence of fractures
Change in body weight Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months Change in body weight
Change in plasma sodium Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in plasma sodium
Change in general well-being Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months Change in general well-being rated on a visual analogue scale reaching from 0 to 10
Incidence of falls Between baseline and visit 3, approximately 3 months Incidence of falls
Change in urinary Prostaglandin- concentration Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months Change in urinary Prostaglandin E2 (PGE2) and metabolite (PGE2M)- concentration
Change in heart rate Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months Change in heart rate
Change in the expression of proteins involved in sodium and water transport Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months Change in the expression of proteins involved in sodium and water transport (AQP2, Prostaglandin transporter (PGT) and NCC) in urinary extracellular vesicles in spot urine (second morning urine)
Change in urine sodium Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in urine sodium
Change in creatinine Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in creatinine
Change in urea Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks Change in urea
Incidence of hyponatremia Between baseline and visit 3, approximately 3 months Incidence of hyponatremia
Trial Locations
- Locations (3)
Hospital Universitario de Móstoles
🇪🇸Móstoles, Spain
University Hospital Basel, Endocrinology, Diabetes and Metabolism
🇨🇭Basel, Switzerland
Kantonsspital Baselland
🇨🇭Liestal, Switzerland